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NIH State-of-the-Science Conference on Symptom Management in
Cancer:
Pain, Depression, and Fatigue
July 15–17, 2002 William H. Natcher Conference Center
National Institutes of Health Bethesda, Maryland
Sponsored by:
♦ National Cancer Institute ♦ Office of Medical Applications of
Research
Cosponsored by:
♦ National Institute on Aging ♦ National Institute of Mental
Health ♦ National Center for Complementary and Alternative Medicine
♦ National Institute of Dental and Craniofacial Research ♦ National
Institute of Neurological Disorders and Stroke ♦ National Institute
of Nursing Research ♦ U.S. Food and Drug Administration
U . S . D E P AR T M E N T O F H E AL T H AN D H U M AN S E R V
I C E S
National Institutes of Health
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Contents
Introduction......................................................................................................................................1
Agenda
.............................................................................................................................................5
Panel
Members...............................................................................................................................11
Speakers
.........................................................................................................................................13
Planning
Committee.......................................................................................................................15
Abstracts
........................................................................................................................................19
I. Introduction and Overview
Methods of the Evidence Report Joseph Lau, M.D.
.........................................................................................................................21
II. Occurrence
Prevalence of Cancer-Related Pain, Depression, and Fatigue
Donald P. Lawrence, M.D.
..........................................................................................................23
Occurrence of Pain Deborah B. McGuire, Ph.D., R.N., F.A.A.N.
.............................................................................25
The Prevalence of Depression in Patients With Cancer Mary Jane
Massie, M.D.
.............................................................................................................29
My Get Up and Go Got Up and Went: Fatigue in People With Cancer
Lillian M. Nail, Ph.D., R.N., C.N.S., F.A.A.N.
...........................................................................31
Occurrence: Symptom Clusters Marylin J. Dodd, Ph.D., R.N.,
F.A.A.N......................................................................................35
III. Assessment
Assessment of Cancer-Related Symptoms: Pain, Depression, and
Fatigue William Pirl,
M.D.........................................................................................................................37
Assessment of Pain in Cancer Charles S. Cleeland, Ph.D.
..........................................................................................................41
Assessment of Depression in Cancer Patients Peter C. Trask,
Ph.D....................................................................................................................43
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III. Assessment (continued)
Assessment of Fatigue in Cancer Patients Paul B. Jacobsen, Ph.D.
...............................................................................................................45
Assessment: Symptom Clusters Judith A. Paice, Ph.D., R.N.,
F.A.A.N.
.......................................................................................47
IV. Treatment
Treatment of Cancer-Related Symptoms: Pain, Depression, and
Fatigue. Relevant Evidence From the Literature Review Daniel B.
Carr, M.D., F.A.B.P.M.
..............................................................................................49
Treatment of Cancer-Related Pain Kathleen M. Foley, M.D.
.............................................................................................................51
Treatment of Depression Michael J. Fisch, M.D.,
M.P.H....................................................................................................53
Evidence-Based Treatment for Cancer-Related Fatigue Victoria
Mock, D.N.Sc., R.N., F.A.A.N.
....................................................................................55
Treatment: Symptom Clusters Stewart B. Fleishman, M.D.
........................................................................................................59
V. Impediments and Suggestions for Solutions
Pain: Impediments and Suggestions for Solutions June L. Dahl,
Ph.D.
......................................................................................................................61
Impediments in the Management of Depression and Suggestions for
Solutions Donna B. Greenberg, M.D.
.........................................................................................................65
Impediments and Solutions to Improving the Management of
Cancer-Related Fatigue Steven D. Passik, Ph.D.
................................................................................................................69
Symptom Clusters: Impediments and Suggestions for Solutions
Susan L. Beck, Ph.D., A.P.R.N., F.A.A.N.
.................................................................................71
VI. Cross-Cutting Issues
Palliative Care in Children and Adolescents. Which Patient Needs
It and When? Michael B. Harris, M.D.
..............................................................................................................75
Symptom Management in the Elderly Cancer Patient Harvey Jay
Cohen, M.D.
.............................................................................................................79
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Introduction
Overview
The National Institutes of Health (NIH) is convening a
State-of-the-Science Conference on Symptom Management in Cancer:
Pain, Depression, and Fatigue, July 15–17, 2002.
Despite advances in early detection and effective treatment,
cancer remains one of the most feared diseases, due not only to its
association with death but with disability. Among the most common
side effects of cancer and treatments for cancer are pain,
depression, and fatigue. It is estimated that as many as 90 percent
of patients will experience pain in the course of their illness.
Between 20 and 40 percent will become depressed and a growing
number will have fatigue that may persist even after treatment
ends. Often these symptoms occur in combination.
While research is producing increasingly hopeful insights into
the causes and cures of cancer, efforts to manage the side effects
of the disease and its treatments have not kept pace. Evidence
suggests that pain is frequently under-treated in the oncology
setting. The increased use of multimodal therapies (e.g., surgery
plus chemotherapy plus radiotherapy), as well as high-dose and
often multidrug regimens to achieve cancer control, is resulting in
more survivors reporting problems with depression and persistent
lack of energy. These symptoms may also be perceived and managed
differently in diverse populations, including the very young, the
elderly, those from low income or educational backgrounds, and
those from ethno-culturally diverse groups.
In the past three decades, scientific discoveries have
transformed cancer from a usually fatal disorder to a curable
illness for some and a chronic disease for many more. With this
shift has come a growing optimism about the future, but also a
growing appreciation of the human costs of cancer care. As patients
live longer with cancer, concern is growing about both the
health-related quality of life of those diagnosed with cancer and
the quality of care they receive. It is currently estimated that
there are 8.9 million individuals living with a history of cancer
in the United States alone. An additional 1,284,900 will be
diagnosed with this disease in 2002, of whom approximately 62
percent can expect to be alive 5 years from now. With the aging of
the population, it can be anticipated that the number of cancer
survivors will continue to grow. Given these figures, addressing
the acute and chronic side effects of cancer on individuals’ lives
is becoming increasingly critical to efforts to reduce the burden
of cancer. The challenge that faces us is how to increase awareness
about the importance of recognizing and actively addressing
cancer-related distress when it occurs. Specifically, we need to be
able to identify who is at risk for cancer-related pain,
depression, and/or fatigue; what treatments work best to address
these symptoms when they occur; and how best to deliver
interventions across the continuum of care.
This two-and-a-half-day conference will examine the current
state of knowledge regarding the management of pain, depression,
and fatigue in individuals with cancer and identify directions for
future research.
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During the first day-and-a-half of the conference, experts will
present the latest research findings on cancer symptom management
to an independent non-Federal panel. After weighing all of the
scientific evidence, the panel will draft a statement addressing
the following key questions:
• What is the occurrence of pain, depression, and fatigue, alone
and in combination, in people with cancer?
• What are the methods used for clinical assessment of these
symptoms throughout the course of cancer, and what is the evidence
for their reliability and validity in cancer patients?
• What are the treatments for cancer-related pain, depression,
and fatigue, and what is the evidence for their effectiveness?
• What are the impediments to effective symptom management in
people diagnosed with cancer, and what are optimal strategies to
overcome these impediments?
• What are the directions for future research?
On the final day of the conference, the panel chairperson will
read the draft statement to the conference audience and invite
comments and questions. A press conference will follow to allow the
panel and chairperson to respond to questions from the media.
The consensus panel’s draft statement will be posted to the
Consensus Program Web site—http://consensus.nih.gov—Wednesday, July
17, 2002.
General Information
Conference sessions will be held in the Natcher Conference
Center, National Institutes of Health, Bethesda, Maryland. Sessions
will run from 8:30 a.m. to 5:30 p.m. on Monday, July 15, from 8:30
a.m. to 12:15 p.m. on Tuesday, July 16, and from 9 a.m. to 11 a.m.
on Wednesday, June 17. A press conference will follow at 1 p.m. The
telephone number for the message center is (301) 594-7302; the fax
number is (301) 480-5982.
Cafeteria
The cafeteria in the Natcher Conference Center is located one
floor above the auditorium on the main floor of the building. It is
open from 7 a.m. to 2 p.m., serving breakfast and lunch.
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Sponsors
The primary sponsors of this meeting are the National Cancer
Institute (NCI) and the Office of Medical Applications of Research
(OMAR) of the National Institutes of Health (NIH). The cosponsors
are the National Institute on Aging (NIA), the National Institute
of Mental Health (NIMH), the National Center for Complementary and
Alternative Medicine (NCCAM), the National Institute of Dental and
Craniofacial Research (NIDCR), the National Institute of
Neurological Disorders and Stroke (NINDS), the National Institute
of Nursing Research (NINR), and the U.S. Food and Drug
Administration (FDA).
Statement of Interest
Each speaker presenting at this conference has been asked to
submit documentation outlining all outside involvement pertaining
to the subject area. Please refer to the chart in your participant
packet for details.
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Agenda
Monday, July 15, 2002
I. Introduction and Overview
8:30 a.m. Opening Remarks Andrew C. von Eschenbach, M.D.
Director National Cancer Institute National Institutes of
Health
8:40 a.m. Charge to the Panel Barnett S. Kramer, M.D., M.P.H.
Director Office of Medical Applications of Research, Office of the
Director National Institutes of Health
8:50 a.m. Conference Overview and Panel Activities Donald L.
Patrick, Ph.D., M.S.P.H. Panel and Conference Chairperson Professor
and Director of Social and Behavioral Sciences Program Department
of Health Services University of Washington
9:00 a.m. Symptoms Richard Payne, M.D. Chief, Pain and
Palliative Care Service and Anne Burnett Tandy Chair in
Neurology
Department of Neurology Memorial Sloan-Kettering Cancer
Center
9:20 a.m. Symptom Clusters Christine Miaskowski, Ph.D., R.N.,
F.A.A.N. Professor and Chair Department of Physiological Nursing
University of California, San Francisco
9:40 a.m. Methods of the Evidence Report Joseph Lau, M.D.
Director Tufts-New England Medical Center Evidence-Based Practice
Center Tufts University School of Medicine
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Monday, July 15, 2002 (continued)
II. Occurrence
10:10 a.m. Prevalence of Cancer-Related Pain, Depression, and
Fatigue. Relevant Evidence From the Literature
Donald P. Lawrence, M.D. Medical Oncologist Division of
Hematology/Oncology Tufts-New England Medical Center Tufts
University School of Medicine
10:25 a.m. Occurrence of Pain Deborah B. McGuire, Ph.D., R.N.,
F.A.A.N. Associate Professor University of Pennsylvania School of
Nursing
10:40 a.m. The Prevalence of Depression in Patients With Cancer
Mary Jane Massie, M.D. Attending Psychiatrist Department of
Psychiatry and Behavioral Sciences Memorial Sloan-Kettering Cancer
Center
10:55 a.m. My Get Up and Go Got Up and Went: Fatigue in People
With Cancer Lillian M. Nail, Ph.D., R.N., C.N.S., F.A.A.N. Dr. May
E. Rawlinson Distinguished Professor and Senior Scientist Director
Center for Research on Symptom Management in Life-Threatening
Illness Oregon Health & Science University School of
Nursing
11:10 a.m. Occurrence: Symptom Clusters Marylin J. Dodd, Ph.D.,
R.N., F.A.A.N. Associate Dean, Academic Affairs Professor,
Department of Physiological Nursing University of California, San
Francisco School of Nursing
11:25 a.m. Discussion
12:05 p.m. Lunch
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Monday, July 15, 2002 (continued)
III. Assessment
1:05 p.m. Assessment of Cancer-Related Symptoms: Pain,
Depression, and Fatigue. Relevant Evidence From the Literature
William Pirl, M.D. Psychiatrist Department of Psychiatry,
Massachusetts General Hospital Tufts University School of
Medicine
1:20 p.m. Assessment of Pain in Cancer Charles S. Cleeland,
Ph.D. McCullough Professor of Cancer Research Director, PAHO/WHO
Collaborating Center in Supportive Cancer Care Chairman, Department
of Symptom Research M.D. Anderson Cancer Center, University of
Texas
1:40 p.m. Assessment of Depression in Cancer Patients Peter C.
Trask, Ph.D. Clinical Associate and Research Investigator
Behavioral Medicine Clinic, Department of Psychiatry University of
Michigan
2:00 p.m. Assessment of Fatigue in Cancer Patients Paul B.
Jacobsen, Ph.D. Program Leader, Psychosocial and Palliative Care
Program Professor, Department of Psychology Moffitt Cancer Center,
University of South Florida
2:20 p.m. Assessment: Symptom Clusters Judith A. Paice, Ph.D.,
R.N., F.A.A.N. Research Professor of Medicine Palliative Care and
Home Hospice Program, Division of Hematology/Oncology Northwestern
University Feinberg Medical School
2:40 p.m. Discussion
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Monday, July 15, 2002 (continued)
IV. Treatment
3:20 p.m. Treatment of Cancer-Related Symptoms: Pain,
Depression, and Fatigue. Relevant Evidence From the Literature
Review
Daniel B. Carr, M.D., F.A.B.P.M. Saltonstall Professor of Pain
Research Medical Director, Pain Management Program Department of
Anesthesia, Tufts-New England Medical Center Tufts University
School of Medicine
3:35 p.m. Treatment of Cancer Related Pain Kathleen M. Foley,
M.D. Society of Memorial Sloan-Kettering Cancer Center Chair in
Pain Research Director, Project on Death in America of the Open
Society Institute Attending Neurologist, Pain and Palliative Care
Service Memorial Sloan-Kettering Cancer Center
3:55 p.m. Treatment of Depression Michael J. Fisch, M.D., M.P.H.
Assistant Professor Symptom Control and Palliative Care M.D.
Anderson Cancer Center, University of Texas
4:15 p.m. Evidence-Based Treatment for Cancer-Related Fatigue
Victoria Mock, D.N.Sc., R.N., F.A.A.N. Associate Professor The
Johns Hopkins University School of Nursing
4:35 p.m. Treatment: Symptom Clusters Stewart B. Fleishman, M.D.
Director Cancer Supportive Services Continuum Cancer Centers of New
York St. Luke’s-Roosevelt Hospital Center Beth Israel Medical
Center Phillips Ambulatory Care Center
4:55 p.m. Discussion
Adjourn around 5:30 p.m.
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Tuesday, July 16, 2002
V. Impediments and Suggestions for Solutions
8:30 a.m. Pain: Impediments and Suggestions for Solutions June
L. Dahl, Ph.D. Executive Director, American Alliance of Cancer Pain
Initiatives Professor, Department of Pharmacology University of
Wisconsin-Madison Medical School
8:45 a.m. Impediments in the Management of Depression and
Suggestions for Solutions Donna B. Greenberg, M.D. Associate
Professor, Psychiatry Harvard Medical School Psychiatry Service,
Medicine Service Massachusetts General Hospital
9:00 a.m. Impediments and Solutions to Improving the Management
of Cancer-Related Fatigue
Steven D. Passik, Ph.D. Director Symptom Management and
Palliative Care Markey Cancer Center, University of Kentucky
9:15 a.m. Symptom Clusters: Impediments and Suggestions for
Solutions Susan L. Beck, Ph.D., A.P.R.N., F.A.A.N. Associate Dean
for Research and Scholarship University of Utah College of
Nursing
9:30 a.m. Discussion
VI. Cross-Cutting Issues
10:00 a.m. Gender Christine Miaskowski, Ph.D., R.N., F.A.A.N.
Professor and Chair Department of Physiological Nursing University
of California, San Francisco
10:20 a.m. Palliative Care in Children and Adolescents. Which
Patient Needs It and When? Michael B. Harris, M.D. Professor of
Pediatrics University of Medicine and Dentistry of New Jersey
Director Tomorrows Children’s Institute Hackensack University
Medical Center
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Tuesday, July 16, 2002 (continued)
VI. Cross-Cutting Issues (continued)
10:40 a.m. Symptom Management in the Elderly Cancer Patient
Harvey Jay Cohen, M.D. Director, Geriatric Research, Education, and
Clinical Center Durham VA Medical Center Chief, Division of
Geriatrics Director, Center for the Study of Aging and Human
Development Department of Medicine Duke University
11:00 a.m. Culture Richard Payne, M.D. Chief, Pain and
Palliative Care Service and Anne Burnett Tandy Chair in
Neurology
Department of Neurology Memorial Sloan-Kettering Cancer
Center
11:20 a.m. Discussion
Adjourn around 12:15 p.m.
Wednesday, July 17, 2002
9:00 a.m. Presentation of the State-of-the-Science Consensus
Statement
9:30 a.m. Public Discussion
11:00 a.m. Panel Meets in Executive Session
1:00 p.m. Press Conference
2:00 p.m. Adjournment
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Panel Members
Panel Chair: Donald L. Patrick, Ph.D., M.S.P.H. Panel and
Conference Chairperson Professor and Director of Social and
Behavioral Sciences Program
Department of Health Services University of Washington Seattle,
Washington
Sandra L. Ferketich, Ph.D., R.N., F.A.A.N.
Dean and Professor College of Nursing University of New Mexico
Albuquerque, New Mexico
Paul S. Frame, M.D. Clinical Professor University of Rochester
School of Medicine Tri-County Family Medicine Cohocton, New
York
Jesse J. Harris, Ph.D. Colonel, U.S. Army (Retired) Dean and
Professor School of Social Work University of Maryland, Baltimore
Baltimore, Maryland
William R. Hazzard, M.D. Professor, Division of Gerontology and
Geriatric Medicine
Department of Medicine University of Washington Seattle VAPSHCS
GRECC Seattle, Washington
Carolyn B. Hendricks, M.D. Medical Oncologist Oncology Care
Associates, P.A. Bethesda, Maryland
Bernard Levin, M.D. Professor Vice President for Cancer
Prevention M.D. Anderson Cancer Center University of Texas Houston,
Texas
Michael P. Link, M.D. Professor of Pediatrics Chief Division of
Pediatric Hematology, Oncology, and Bone Marrow Transplantation
Stanford University Medical Center Stanford, California
Craig Lustig, M.P.A. Communications Specialist University of
Maryland Center on Aging College Park, Maryland
Joseph McLaughlin, Ph.D. President International Epidemiology
Institute Rockville, Maryland
L. Douglas Ried, Ph.D. Associate Professor Pharmacy Health Care
Administration College of Pharmacy University of Florida
Gainesville, Florida
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Andrew T. Turrisi III, M.D. Professor and Chair Radiation
Oncology Medical University of South Carolina Charleston, South
Carolina
Jürgen Unützer, M.D., M.P.H. Associate Professor-in-Residence
Department of Psychiatry and Biobehavioral Sciences
Neuropsychiatric Institute University of California, Los Angeles
School of Medicine
Los Angeles, California
Sally W. Vernon, Ph.D. Professor of Epidemiology and Behavioral
Sciences
Center for Health Promotion and Prevention Research
School of Public Health University of Texas at Houston Houston,
Texas
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Speakers
Susan L. Beck, Ph.D., A.P.R.N., F.A.A.N. Associate Dean for
Research and Scholarship University of Utah College of Nursing Salt
Lake City, Utah
Daniel B. Carr, M.D., F.A.B.P.M. Saltonstall Professor of Pain
Research Medical Director, Pain Management Program Department of
Anesthesia Tufts-New England Medical Center Boston,
Massachusetts
Charles S. Cleeland, Ph.D. McCullough Professor of Cancer
Research Director, PAHO/WHO Collaborating Center in Supportive
Cancer Care
Chairman, Department of Symptom Research M.D. Anderson Cancer
Center University of Texas Houston, Texas
Harvey Jay Cohen, M.D. Director, Geriatric Research, Education,
and Clinical Center
Durham VA Medical Center Chief, Division of Geriatrics Director,
Center for the Study of Aging and Human Development
Department of Medicine Duke University Durham, North
Carolina
June L. Dahl, Ph.D. Executive Director American Alliance of
Cancer Pain Initiatives Professor Department of Pharmacology
University of Wisconsin-Madison Medical School
Madison, Wisconsin
Marylin J. Dodd, Ph.D., R.N., F.A.A.N. Associate Dean, Academic
Affairs Professor Department of Physiological Nursing University of
California, San Francisco School of Nursing
San Francisco, California
Michael J. Fisch, M.D., M.P.H. Assistant Professor Symptom
Control and Palliative Care M.D. Anderson Cancer Center University
of Texas Houston, Texas
Stewart B. Fleishman, M.D. Director, Cancer Supportive Services
Continuum Cancer Centers of New York St. Luke’s-Roosevelt Hospital
Center Beth Israel Medical Center Phillips Ambulatory Care Center
New York, New York
Kathleen M. Foley, M.D. Society of Memorial Sloan-Kettering
Cancer Center Chair in Pain Research
Director, Project on Death in America of the Open Society
Institute
Attending Neurologist Pain and Palliative Care Service Memorial
Sloan-Kettering Cancer Center New York, New York
Donna B. Greenberg, M.D. Associate Professor, Psychiatry Harvard
Medical School Psychiatry Service Medicine Service Massachusetts
General Hospital Boston, Massachusetts
Michael B. Harris, M.D. Professor of Pediatrics University of
Medicine and Dentistry of New Jersey
Director Tomorrows Children’s Institute Hackensack University
Medical Center Hackensack, New Jersey
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Paul B. Jacobsen, Ph.D. Program Leader, Psychosocial and
Palliative Care Program
Professor, Department of Psychology Moffitt Cancer Center
University of South Florida Tampa, Florida
Joseph Lau, M.D. Director Tufts-New England Medical Center
Evidence-Based Practice Center
Tufts University School of Medicine Boston, Massachusetts
Donald P. Lawrence, M.D. Medical Oncologist Division of
Hematology/Oncology Tufts-New England Medical Center Tufts
University School of Medicine Boston, Massachusetts
Mary Jane Massie, M.D. Attending Psychiatrist Department of
Psychiatry and Behavioral Sciences
Memorial Sloan-Kettering Cancer Center New York, New York
Deborah B. McGuire, Ph.D., R.N., F.A.A.N. Associate Professor
University of Pennsylvania School of Nursing
Philadelphia, Pennsylvania
Christine Miaskowski, Ph.D., R.N., F.A.A.N.
Professor and Chair Department of Physiological Nursing
University of California, San Francisco San Francisco,
California
Victoria Mock, D.N.Sc., R.N., F.A.A.N. Associate Professor The
Johns Hopkins University School of Nursing
Baltimore, Maryland
Lillian M. Nail, Ph.D., R.N., C.N.S., F.A.A.N.
Dr. May E. Rawlinson Distinguished Professor and Senior
Scientist
Director Center for Research on Symptom Management in
Life-Threatening Illness
Oregon Health & Science University School of Nursing
Portland, Oregon
Judith A. Paice, Ph.D., R.N., F.A.A.N. Research Professor of
Medicine Palliative Care and Home Hospice Program
Division of Hematology/Oncology Northwestern University Feinberg
Medical School
Chicago, Illinois
Steven D. Passik, Ph.D. Director, Symptom Management and
Palliative Care
Markey Cancer Center University of Kentucky Lexington,
Kentucky
Richard Payne, M.D. Chief, Pain and Palliative Care Service Anne
Burnett Tandy Chair in Neurology Department of Neurology Memorial
Sloan-Kettering Cancer Center New York, New York
William Pirl, M.D. Psychiatrist Department of Psychiatry
Massachusetts General Hospital Boston, Masachusetts
Peter C. Trask, Ph.D. Clinical Associate Research Investigator
Behavioral Medicine Clinic Department of Psychiatry University of
Michigan Ann Arbor, Michigan
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Planning Committee
Planning Committee Chairs:
Julia H. Rowland, Ph.D. Director, Office of Cancer Survivorship
Division of Cancer Control and
Population Sciences National Cancer Institute National
Institutes of Health Bethesda, Maryland
Claudette Varricchio, D.S.N., R.N., F.A.A.N.
Chief Office of Extramural Programs National Institute of
Nursing Research National Institutes of Health Bethesda,
Maryland
John A. Bowersox Communications Specialist Office of Medical
Applications of Research Office of the Director National Institutes
of Health Bethesda, Maryland
Patricia S. Bryant, Ph.D. Program Director Behavior and Health
Promotion Research Office of Clinical, Behavioral, and Health
Promotion Research
National Institute of Dental and Craniofacial Research
National Institutes of Health Bethesda, Maryland
Margaret Coopey, R.N., M.G.A., M.P.S. Health Policy Analyst
Center for Practice and Technology Assessment
Agency for Healthcare Research and Quality
U.S. Department of Health and Human Services
Rockville, Maryland
Jerry M. Elliott Program Analysis and Management Officer Office
of Medical Applications of Research Office of the Director National
Institutes of Health Bethesda, Maryland
Stewart B. Fleishman, M.D. Director, Cancer Supportive Services
Continuum Cancer Centers of New York St. Luke’s-Roosevelt Hospital
Center Beth Israel Medical Center Phillips Ambulatory Care Center
New York, New York
Donna J. Griebel, M.D. Medical Officer Division of Oncology Drug
Products Office of Review Management Center for Drug Evaluation and
Research U.S. Food and Drug Administration Rockville, Maryland
Paul B. Jacobsen, Ph.D. Program Leader, Psychosocial and
Palliative Care Program
Professor, Department of Psychology Moffitt Cancer Center
University of South Florida Tampa, Florida
Cheryl Kitt, Ph.D. Program Director Pain, Neuroendocrinology,
and Neurotoxicology Research
Systems and Cognitive Neuroscience National Institute of
Neurological Disorders and Stroke
National Institutes of Health Bethesda, Maryland
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Barnett S. Kramer, M.D., M.P.H. Director Office of Medical
Applications of Research Office of the Director National Institutes
of Health Bethesda, Maryland
Joseph Lau, M.D. Director Tufts-New England Medical Center
Evidence-Based Practice Center
Tufts University School of Medicine Boston, Massachusetts
Christine Miaskowski, Ph.D., R.N., F.A.A.N.
Professor and Chair Department of Physiological Nursing
University of California, San Francisco San Francisco,
California
Peter Muehrer, Ph.D. Chief, Health and Behavioral Science
Research Branch
Division of Mental Disorders, Behavioral Research, and AIDS
National Institute of Mental Health National Institutes of
Health Bethesda, Maryland
Karen Patrias, M.L.S. Senior Resource Specialist Public Services
Division National Library of Medicine National Institutes of Health
Bethesda, Maryland
Donald L. Patrick, Ph.D., M.S.P.H. Panel and Conference
Chairperson Professor and Director of Social and Behavioral
Sciences Program
Department of Health Services University of Washington Seattle,
Washington
Richard Payne, M.D. Chief, Pain and Palliative Care Service Anne
Burnett Tandy Chair in Neurology Department of Neurology Memorial
Sloan-Kettering Cancer Center New York, New York
Janice Phillips, Ph.D., R.N., F.A.A.N. Program Director Health
Promotion and Risk Behaviors Office of Extramural Programs National
Institute of Nursing Research National Institutes of Health
Bethesda, Maryland
Brad H. Pollock, Ph.D., M.P.H. Professor Department of
Pediatrics University of Texas Health Science Center at San
Antonio
San Antonio, Texas
Mary Ann Richardson, Dr.P.H., M.P.H. Program Officer National
Center for Complementary and Alternative Medicine
National Institutes of Health Bethesda, Maryland
Susan Rossi, Ph.D., M.P.H. Deputy Director Office of Medical
Applications of Research Office of the Director National Institutes
of Health Bethesda, Maryland
Edward Trimble, M.D., M.P.H. Head, Surgery Section Clinical
Investigation Branch Cancer Therapy Evaluation Program Division of
Cancer Treatment and Diagnosis
National Cancer Institute National Institutes of Health
Bethesda, Maryland
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Rosemary Yancik, Ph.D. Chief, Cancer Section Geriatrics Program
National Institute on Aging National Institutes of Health Bethesda,
Maryland
Marcia Zorn, M.A., M.L.S. Librarian Public Services Division
National Library of Medicine National Institutes of Health
Bethesda, Maryland
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Abstracts
The following are abstracts of presentations to the NIH
State-of-the-Science Conference on Symptom Management in Cancer:
Pain, Depression, and Fatigue. They are designed for the use of
panelists and participants in the conference and as a reference
document for anyone interested in the conference deliberations. We
are grateful to the authors for their participation and for
supplying these summaries.
Abstracts for the following presentations do not appear:
Symptoms—Richard Payne, M.D.
Symptom Clusters–Christine Miaskowski, Ph.D., R.N., F.A.A.N.
Gender—Christine Miaskowski, Ph.D., R.N., F.A.A.N.
Culture—Richard Payne, M.D.
Julia H. Rowland, Ph.D. Director, Office of Cancer Survivorship
Division of Cancer Control and
Population Sciences National Cancer Institute National
Institutes of Health
Claudette Varricchio, D.S.N., R.N., F.A.A.N. Program Director
Nurse Consultant Division of Cancer Prevention National Cancer
Institute National Institutes of Health
Cynthia A. Rooney Program Analyst Office of Medical Applications
of Research Office of the Director National Institutes of
Health
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Methods of the Evidence Report
Joseph Lau, M.D.
The Office of Medical Applications of Research (OMAR) at the
National Institutes of Health (NIH) requested that the Agency for
Healthcare Research and Quality (AHRQ), through its Evidence-Based
Practice Center (EPC) program, produce an evidence report on the
topic of Symptom Management in Cancer: Pain, Depression, and
Fatigue for this State-of-the-Science Conference. The New England
Medical Center EPC produced this evidence report based on a
systematic review of the literature summarizing evidence in several
key areas identified by the conference planning committee. The
clinical conditions covered in this report include cancer-related
pain, depression, and fatigue. The issues addressed for each of
these conditions in this report include prevalence, assessment, and
treatment.
Evidence reports review relevant scientific literature on
assigned clinical care topics and produce evidence reports and
technology assessments, conduct research on methodologies and the
effectiveness of their implementation, and participate in technical
assistance activities. Public and private sector organizations may
use the reports and assessments as the basis for their own clinical
guidelines and other quality improvement activities.
The various combinations of symptoms and issues identified by
the planning committee create nine distinct topics, several of
which are very broad in nature and encompass many interrelated
issues. Addressing each of the nine topics fully is beyond the
scope of this evidence report. Supplementing the information in our
evidence report, speakers will be invited to discuss topics of
their expertise at the State-of-the-Science Conferences. This
evidence report is structured according to the following
topics:
• Prevalence of cancer-related pain • Prevalence of
cancer-related depression • Prevalence of cancer-related fatigue •
Assessment of cancer-related pain • Assessment of cancer-related
depression • Assessment of cancer-related fatigue • Treatment of
cancer-related pain • Treatment of cancer-related depression •
Treatment of cancer-related fatigue
For some of these topics, in particular the treatment of cancer
pain, there are multiple questions. Our EPC previously produced the
evidence report on the Management of Cancer Pain based on a
literature search conducted in December 1998. For the
cancer-related pain topics, the results for the key questions
addressed in the prior report have been thoroughly updated. At the
request of the conference planning committee, we added two new
topics to the treatment of cancer-related pain (oral mucositis and
post-herpetic neuralgia) in this report. We have summarized the
methodological approach and reported the new evidence. Readers are
referred to
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the earlier evidence report for detailed information. New
systematic reviews are also included for the symptoms of
cancer-related depression and cancer-related fatigue.
Literature Search
Literature searches were conducted to identify studies published
between 1966 and 2001. For cancer pain, we applied the same search
strategy used in our previously published Management of Cancer Pain
evidence report to identify new studies published from December
1998 through June 2001. The National Library of Medicine, as a
partner in the State-of-the-Science conference process, with input
from the EPC staff, performed the literature search for
cancer-related depression and cancer-related fatigue. The searches
were supplemented with reviews of bibliographies of selected
references. We also identified published meta-analyses and used
their data for selected topics.
Selection Criteria
We accepted all studies that addressed the issues of prevalence,
assessment, or treatment in patients with a diagnosis of cancer who
suffered from pain, depression, or fatigue due to cancer or
treatment of cancer. We placed no restrictions on the patients’
age, gender, ethnicity, and stage of the primary disease or
presence of metastases.
For estimating the prevalence of cancer-related symptoms, we
used only studies that assessed the prevalence of the symptom as
the primary purpose of the study. For assessment, both
retrospective and prospective studies were used, as well as
randomized and nonrandomized trials and cross-sectional and
longitudinal studies. Randomized controlled trials were used to
analyze efficacy of interventions.
Summarizing the Literature
We incorporated over 200 English language articles in the
evidence report. Specific inclusion criteria and methods of
synthesis were developed for each of the topics. Relevant data from
each article were abstracted into evidence tables. Information from
the evidence tables was synthesized into summary tables describing
the findings of each study.
The nine topics addressed in this evidence report are presented
in the order of prevalence, assessment, and treatment. Each of
these issues covers the symptoms of pain, depression, and fatigue.
Evidence is summarized using three complementary approaches.
Evidence tables provide detailed information about the
characteristics and outcomes of all the studies examined.
Information from the evidence tables was synthesized into summary
tables describing the findings of each study. A narrative
description of the studies along with an evidence-grading scheme
accompanies the summary tables.
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Prevalence of Cancer-Related Pain, Depression, and Fatigue
Donald P. Lawrence, M.D.
An evidence report on the topic of “Symptom Management in
Cancer: Pain, Depression, and Fatigue” was requested by the Office
of Medical Applications of Research of the National Institutes of
Health for a State-of-the-Science Conference. As requested by the
planning committee of this conference, a systematic review of the
medical literature on the prevalence of cancer-related pain,
fatigue, and depression was performed as part of this evidence
report. The methodology used to produce this report is described
elsewhere.
Cancer-Related Pain
Twenty-nine studies on the prevalence or incidence of
cancer-related pain were identified and summarized for this report.
The minimum prevalence or incidence rate of pain reported in these
studies was 14 percent. Surveillance data on the incidence and
prevalence of cancer, and observational and survey data on the
incidence of cancer-related pain, indicate that a majority of
patients will experience pain at some point during their course and
that cancer pain impairs quality of life and functionality. This
disturbing finding reflects data from developed countries, often in
tertiary care or in specialist consultative settings. The
likelihood of pain increases, as does its severity, with advancing
cancer stage. Pain is generally not eliminated despite analgesic
therapy administered according to the World Health Organization
method for cancer pain relief, and it may continue to be a problem
even after eradication of the underlying neoplasia.
Future Research: Multiple processes underlie cancer-related
pain, yet survey data only now are beginning to distinguish between
different etiologies and mechanisms. Additional research is
required to provide a comprehensive picture of pain course over the
continuum of care, and of the relationship between effectiveness of
pain control and quality of life. Minorities, women, and the
elderly may be at greater risk for undertreatment of cancer pain,
and these issues should be the subjects of future research.
Cancer-Related Depression
Although depressive symptoms are present in several psychiatric
disorders, the ones most commonly seen in people with cancer are
major depressive disorder, adjustment disorder with depressed mood,
and mood disorder secondary to general medical condition.
Depressive symptoms may also occur in the absence of a psychiatric
disorder. Because major depressive disorder is the best described
in the literature, 12 studies were reviewed that used Diagnostic
and Statistical Manual of Mental Disorders (DSM) criteria to
identify the rate of major depressive disorder in cancer patients.
The rate ranged from 10 to 25 percent in the majority of these
studies. In addition, studies of clinically significant depressive
symptoms regardless of psychiatric diagnosis were reviewed. A
variety of assessment instruments were utilized, making comparisons
of the reported rates of depressive symptoms problematic. The
review was therefore limited to 15 studies that employed the
Hospital Anxiety and Depression Scale (HADS), the
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most commonly used instrument. The rates of clinically
significant depressive symptoms ranged from 7 to 21 percent in the
majority of these studies. In contrast to prevalence studies, no
studies were identified that examined the incidence of major
depressive disorder in patients with cancer. Many studies, however,
contained information on the incidence of clinically significant
depressive symptoms in cancer patients. The review was again
limited to five studies that employed the HADS, the most widely
utilized instrument. The incidence rate of depressive symptoms was
1.8–7.4 percent per year in these studies.
Future Research: A large number of variables may affect the
rates of depressive disorders and depressive symptoms in cancer
patients, including medical and sociodemographic factors as well as
the method and timing of the assessment. Further research is needed
to determine the influence of such variables and the prevalence of
depression associated with specific types of cancer and cancer
treatment. Predictive models to determine which cancer patients are
at risk for depression would be of value.
Cancer-Related Fatigue
Twenty-seven studies were identified that reported prevalence
rates of cancer-related fatigue in the setting of many types of
cancer treatment, in patients receiving palliative care, and in
cancer survivors, but the data is by no means comprehensive. Many
types of cancer were not specifically addressed. A very broad range
of prevalence rates was reported, from 4 percent in breast cancer
prior to starting chemotherapy and 8 percent in prostate cancer
prior to radiation therapy to 91 percent in breast cancer patients
after surgery and chemotherapy and before bone marrow
transplantation. Findings of significant concern were the high
rates of fatigue in cancer survivors: 26 percent in Hodgkin’s
disease survivors, 35–56 percent in breast cancer survivors, and 48
percent in a cohort treated for various cancers.
Comparisons of the prevalence rates between studies are
problematic because each study used different criteria for defining
the presence or absence of fatigue and its severity. Most studies
measured fatigue at only one time point during treatment or
remission, or at a limited number of time points associated with a
particular cancer treatment. There were no longitudinal studies of
cancer fatigue. Fatigue may have been systematically underestimated
in studies using selected cohorts because the most fatigued
patients may have been unable to participate. There have been few
population-based studies of the prevalence of cancer fatigue.
Future Research: More comprehensive assessments are needed of
the prevalence of fatigue in a wider variety of cancer types and
settings. Additional population-based as well as longitudinal
studies are needed. Useful data on the prevalence of fatigue can
potentially be extracted from studies of health-related quality of
life, general symptom surveys, and treatment trials. However,
methods to compare results from studies that employ different
assessment instruments must be devised.
Research is also needed on the potential interactions between
pain, depression, and fatigue (as well as other cancer symptoms)
and their impact on health-related quality of life. The influence
of gender and cultural factors on patients’ experience of cancer
symptoms and on how these symptoms are diagnosed and treated is
another important area for future exploration.
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Occurrence of Pain
Deborah B. McGuire, Ph.D., R.N., F.A.A.N.
Occurrence of pain in people with cancer is highly variable and
incompletely understood because of the multiple factors involved
and because of the difficulties in studying it. Researchers have
attempted to conduct incidence and prevalence surveys, but much of
their work is not population-based and is characterized by small
and often heterogeneous samples; variable pain assessment
techniques; and incomplete information about etiology of pain,
types of pain syndromes, and clinical and/or demographic
factors.
Cancer-related pain is generally acknowledged to consist of
three major categories: (1) pain caused by direct tumor
involvement, (2) pain that results from diagnostic or therapeutic
procedures, and (3) pain that is caused by side effects or
toxicities of cancer treatment. These categories can be further
subdivided into syndromes and/or subtypes, each of which has
specific characteristics with respect to manifestations, temporal
nature, defining qualities, and so on. Moreover, it is common for a
single individual to have more than one type of cancer-related pain
at the same time, and for pain to wax and wane throughout the
course of cancer.
Taking this complexity into account, it is obvious why a
complete understanding of the occurrence of cancer-related pain
remains elusive. It is rare for researchers to report on specific
types of cancer pain in their samples. Nevertheless, existing data
do provide insight into the occurrence of pain. Incidence and
prevalence rates range from 14 to 100 percent, and between
one-third to one-half of people with cancer will experience pain at
some point in their cancer trajectory. Careful analysis of existing
studies reveals numerous patterns of occurrence, depending on the
patient population, study methodology, instruments used to assess
pain, and other factors. The majority of incidence or prevalence
studies have focused on people with types of cancer most commonly
associated with pain, for instance, breast, lung, and prostate, or
with solid tumors in general.
Most researchers report a variety of cancers in their samples,
with little attempt to delineate incidence or prevalence according
to specific type of cancer. And although most of the investigators
do not specifically report whether pain is caused by direct tumor
involvement, it can probably be safely assumed that this is the
case. No study reported a rate of less than 14 percent, and many
reported ranges such as 43–80 percent;(1) 38–60 percent;(2)
54–92 percent;(3) or 63–90 percent.(4) Rates seem to be somewhat
higher (e.g., 70–100 percent) in settings that focused on
palliative care or pain management.(5,6)
Few researchers have conducted studies that focused solely on
pain caused by diagnostic or therapeutic procedures, generally
preferring to report statistics on both tumor and
diagnostic/treatment pain. In one such study, only about half of
the patients had pain related to treatment, while over half had
both tumor- and treatment-related pain or treatment-related pain
alone. A few investigators have reported rates of pain occurrence
for specific populations, for
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example, a 20 percent rate of postmastectomy pain.(7) Still
fewer researchers have devoted themselves to obtaining occurrence
data on pain that is caused by specific cancer treatment side
effects or toxicities. A notable example is the acute oral pain
that is caused by mucositis, a treatment side effect, with some
rates as high as 100 percent in certain patient populations.(8)
Existing studies have several important characteristics. For
instance, although the majority of studies have been conducted in
the United States, several large international studies have
examined rates of pain, yielding essentially similar results to
those in the U.S. studies. Only a few studies have included
minority groups or others at particular risk of pain, such as the
elderly or women. Still others have focused on specific types of
pain, such as transitory or breakthrough pain. And some authors
have carefully followed pain over time to determine its course,
severity, impact on quality of life and functional status, and
other related factors.(5)
Recommendations for future research include the need to acquire
further specific information on the occurrence of pain in a variety
of cancer diagnoses, settings, and groups of people. These studies
will serve to increase our understanding of the scope and nature of
the occurrence of pain. It is often difficult to determine the
precise characteristics of cancer-related pain in a given sample
because of aggregate reporting and lack of specific information
broken down by type of cancer, stage, type of cancer pain, and
other factors. However, linking these critical areas of information
will improve our understanding of pain and enhance our ability to
fashion appropriate and clinically salient interventions, thereby
increasing patients’ quality of lives.
References
1. Vainio A, Auvinen A. Prevalence of symptoms among patients
with advanced cancer in an international collaborative study.
Symptom Prevalence Group. J Pain Symptom Manage
1996;12(1):3–10.
2. Greenwald HB, Bonica JJ, Bergner M. The prevalence of pain in
four cancers. Cancer 1987;60(10):2563–9.
3. Petzke F, Radbruch L, Zech D, et al. Temporal presentation of
chronic cancer pain: Transitory pains on admission to a
multidisciplinary pain clinic. J Pain Symptom Manage
1999;17(6):391–401.
4. Higginson IJ, Hearn J. A multicenter evaluation of cancer
pain control by palliative care teams. J Pain Symptom Manage
1997;14(1):29–35.
5. Brescia FJ, Portenoy RK, Ryan M, et al. Pain, opioid use, and
survival in hospitalized patients with advanced cancer. J Clin
Oncol 1992;10(1):149–55.
6. Coyle N, Adelhardt J, Foley KM, et al. Character of terminal
illness in the advanced cancer patient: Pain and other symptoms
during the last four weeks of life. J Pain Symptom Manage
1990;5(2):83–93.
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7. Stevens PE, Dibble SL, Miaskowski C. Prevalence,
characteristics, and impact of postmastectomy pain syndrome: An
investigation of women’s experiences. Pain 1995;61(1):61–8.
8. McGuire DB, Altomonte V, Peterson DE, et al. Patterns of
mucositis and pain in patients receiving preparative chemotherapy
and bone marrow transplantation. Oncol Nurs Forum
1993;20(10):1493–502.
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The Prevalence of Depression in Patients With Cancer
Mary Jane Massie, M.D.
Americans have a one in five chance of developing depression in
their lifetimes. Depression is at least twice as common in patients
with several medical or neurological illnesses. The clinical “rule
of thumb” is that 25 percent of cancer patients are likely
depressed enough at some point in the course of disease to warrant
evaluation and treatment.
Depression is the psychiatric syndrome that has received the
most attention in individuals with cancer. Depression has been
challenging to study because symptoms occur on a spectrum that
ranges from sadness to major affective disorder, and mood change is
often difficult to evaluate when a patient is confronted by
repeated threats to life, is receiving cancer treatments, is
fatigued, and/or is experiencing pain.
Although many research groups have assessed depression in cancer
patients since the 1960s, the reported prevalence (major depression
0–38 percent; depression spectrum syndromes 0–58 percent) varies
significantly because of varying conceptualizations of depression,
different criteria used to define depression, differences in
methodological approaches to the measurement of depression, and
different populations studied (i.e., hospitalized patients who had
just completed a disfiguring surgery that led to a cancer
diagnosis; patients awaiting a bone marrow transplant that has
significant morbidity and mortality; patients without evidence of
disease and likely cured, evaluated at an annual medical oncology
clinic followup visit, etc.). The methods (self-report, brief
screening instruments, and structured clinical interviews) most
commonly used were the HADS, BDI, EORTC-QLQ-C30, and DSM III
criteria. Effects of cancer treatments and non-cancer related
variables that affect mood often are not accounted for in these
studies.
In early, usually cross-sectional studies, the rate of
depression was usually reported for adults with all types and
stages of cancer.(1,2) Depression was reported by severity
(borderline, mild, moderate, severe), by a symptom such as
depressed mood, or by some of these diagnostic categories: major
depression, minor depression, depressive disorder, adjustment
disorder with depressed mood, or dysthymia. Most research groups
reported the gender and age (usually older) of study subjects, but
findings often were not reported by demographic variables.
Minorities were always underrepresented in these studies.
A meta-analysis of 58 studies conducted from 1980 to 1994
demonstrated that cancer patients were significantly more depressed
than the normal population and that there were significant
differences among groups with regard to sex, age, and type of
cancer.(3) Another review of 49 studies of depression in cancer
patients revealed no gender differences, although the prevalence of
depression in women is greater than the prevalence in men.(4)
Cancer types highly associated with depression are oropharyngeal
(22–57 percent), pancreas (33–50 percent), breast (4.5–46 percent)
and lung (11–44 percent). A less high prevalence of depression is
reported in patients with other cancers, such as colon (13–25
percent), gynecological (12–23 percent), and lymphoma (8–19
percent). It is unclear whether the particularly high rates of
depression reported for some cancers (i.e.,
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oropharyngeal and pancreatic) are related to treatment side
effects or the pathophysiology of the (5) tumor.
Conclusions
The are over 100 studies of the prevalence of depression in
cancer patients. The occurrence of depression is significant, and
challenges remain for the assessment of depression in cancer
patients. Future research must focus on establishing diagnostically
reliable criteria, developing standard instruments for measuring
depression, characterizing the causative role of antineoplastics in
depression, and identifying biological markers for depression.
References
1. Derogatis LR, Morrow GR, Fetting J. The prevalence of
psychiatric disorders among cancer patients. JAMA
1983;249:751–7.
2. Bukberg J, Penman D, Holland JC. Depression in hospitalized
cancer patients. Psychosom Med 1984;46:199–212.
3. van’t Spijker A, Trijsburg RW, Duivenvoorden HJ.
Psychological sequelae of cancer diagnosis: a meta-analytical
review of 58 studies after 1980. Psychosom Med 1997;59:280–93.
4. DeFlorio ML, Massie MJ. Review of depression in cancer:
gender differences. Depression 1995;3:66–80.
5. Newport DJ, Nemeroff CB. Assessment and treatment of
depression in the cancer patient. J Psychosom Res
1998;45(3):215–37.
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My Get Up and Go Got Up and Went: Fatigue in People With
Cancer
Lillian M. Nail, Ph.D., R.N., C.N.S., F.A.A.N.
Prior to the mid-1980s, fatigue was rarely addressed in the
literature on the symptom experience of people with cancer. The
massive interest in fatigue that began in the early 1990s has
produced a significant body of research and has fostered the
development of guidelines for assessing and managing fatigue.
Despite this high level of activity, there are a number of gaps in
knowledge about fatigue in people with cancer that need to be
addressed in order to support clinical practice.
Information on the incidence and prevalence of fatigue in people
with cancer is based on incidental findings of cancer treatment
studies, studies of the psychosocial aspects of cancer and cancer
treatment, and studies of the pattern and characteristics of
fatigue during cancer treatment. The majority of studies address
fatigue during single modality treatment for localized or regional
disease. Results vary according to the type of cancer treatment,
point in treatment when fatigue is assessed, and the approach used
for defining the occurrence of fatigue. The common finding across
these diverse studies is that fatigue is experienced by 50 to 100
percent of people undergoing cancer treatment. High-dose interferon
therapy for malignant melanoma is an example of severe fatigue that
was dose-limiting.
The longitudinal studies of people undergoing specific types of
cancer treatment demonstrate a pattern of fatigue that is
treatment-related, as the sensation of tiredness increases over the
course of treatment and decreases following the completion of
treatment. The cyclic treatment schedules seen in many standard
cancer chemotherapy regimens produce a cyclic pattern of fatigue,
while traditional external beam radiation treatment produces a
pattern of steady increase in fatigue with a peak near the
completion of treatment. There is little information on demographic
or clinical variables associated with risk for fatigue during
cancer treatment. Very few studies have addressed the experience of
children with cancer; however, the recent work on this topic
demonstrates that children also experience fatigue as a side effect
of cancer treatment. The results of the longitudinal treatment
studies provide the content for the preparatory information
provided to people about to start treatment and guide the timing of
clinical assessment.
Many different mechanisms are suggested as contributing to
fatigue during cancer treatment. Some of the hypothesized
mechanisms include anemia, muscle mass loss, nutritional deficits,
hormone shifts, accumulation of products of cell death, specific
cytokines released as a response to immune suppression or as part
of the immune response, dehydration, sleep disruption, and changes
in neurotransmitter levels or function. Chemotherapy-induced anemia
is the only one that has been studied in the depth required to
demonstrate that it does cause fatigue.
Fatigue has also been identified as a persistent side effect
following cancer treatment. Although research on this topic is just
beginning, type of treatment is believed to be an important factor,
with persistent fatigue identified as a key quality of life issue
in long-term survivors, and the prevalence of persistent fatigue is
estimated at 10 percent among women who have
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completed adjuvant therapy for breast cancer. Longitudinal
studies are needed in order to characterize the incidence,
prevalence, pattern, risk factors, and correlates of persistent
fatigue in adults and to determine if persistent fatigue occurs in
children.
A major gap in knowledge about fatigue in people with cancer is
about the role of cancer as a cause of fatigue. It is difficult to
separate the effects of treatment from the effects of cancer
because there are few untreated people with cancer; most fatigue
studies have accrued subjects with no evidence of disease; and
studies of people with advanced cancer are difficult to interpret
because of multiple confounding factors (i.e., cachexia,
dehydration, side effects of analgesics, decreased physical
activity, and/or abnormal liver function). However, the studies of
symptoms in people with advanced cancer referred for palliative
care indicate that not all of them report fatigue. This finding
challenges a long tradition of listing fatigue as a presenting
symptom of cancer and viewing “having cancer” as a sufficient
explanation for the fatigue reported by people with cancer. The
specific situations in which fatigue is likely to be seen as a
presenting symptom of cancer need to be defined, and evaluation of
the independent contribution of tumor burden to fatigue should be
considered in future work on mechanisms of fatigue in people with
cancer.
A similar challenge is posed by the belief that fatigue is
solely an indicator of depression. Examining the relationship
between feelings of sadness and symptoms is difficult because of
the issues of temporal precedence, where fatigue and depression can
occur together because fatigue is an indicator of depression or
because feeling tired all the time makes one feel sad. When
analyses have been conducted to address this question, the findings
indicate that fatigue should not be considered diagnostic of
clinical depression in people with cancer undergoing active
treatment. Further research is needed to determine if the same
patterns of relationships exist following treatment and in advanced
cancer and to understand the extent to which clarifying the
relationship between these two symptoms can improve symptom
management.
Fatigue is now recognized as the most common side effect of
cancer treatment. The patterns of fatigue associated with the most
common forms of cancer treatment in adults have been described, and
research on fatigue that persists beyond the completion of
treatment is growing. These studies indicate the need for
assessment and management of fatigue throughout cancer treatment
and during followup care. Knowledge about mechanisms of fatigue is
needed to address prevention and management, to target the
identification of high-risk groups, and to provide answers to basic
questions about the occurrence of fatigue in people with
cancer.
References
Andrykowski MA, Curran SL, Lightner R. Off-treatment fatigue in
breast cancer survivors: a controlled comparison. J Behav Med
1998;21:1–18.
Demetri GD, Kris M, Wade J, Degos L, Cella D. Quality-of-life
benefit in chemotherapy patients treated with Epoetin Alfa is
independent of disease response or tumor type: results from a
prospective community oncology study. J Clin Oncol
1998;16:3412–25.
Mock V, Barsevick A, Cella D, Cimprich B, Cleeland C, Donnelly
J, Eisenberger MA, Escalante C, Hinds P, Jacobsen PB, Kaldor P,
Knight SJ, Peterman A, Piper BF, Rugo H,
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Sabbatini P, Stahl C. NCCN practice guidelines for
cancer-related fatigue. Oncology (Huntington)
2000;14(11A):151–61.
Nail LM. Fatigue in patients with cancer. Oncol Nurs Forum
2002;29:537–46.
Winningham ML, Nail LM, Burke MB, Brophy L, Cimprich B, Jones
LS, Pickard-Holley S, Rhodes V, St. Pierre B, Beck S, et al.
Fatigue and the cancer experience: the state of the knowledge.
Oncol Nurs Forum 1994;21:23–36.
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Occurrence: Symptom Clusters
Marylin J. Dodd, Ph.D., R.N., F.A.A.N., and Christine
Miaskowski, Ph.D., R.N., F.A.A.N.
Introduction
Determining the occurrence/prevalence of “symptom clusters” in
persons with cancer rests squarely with attempts at defining the
term. This presentation will report on a search of the cancer
literature using the key term “symptom cluster” and similar terms
(“symptom constellation” or “symptom combinations”) and the
challenges encountered. Foremost in these challenges is the current
definition of these terms. Another challenge is the diverse roles
that coexisting, correlated symptoms have played in data-based
studies, ranging from predictors of patient outcomes to outcomes
themselves.
Background
It was noted that the occurrence of coexisting symptoms led to
greater patient morbidity in a sample of elderly patients with
cancer who had undergone surgery. This finding has been tested by
other groups of investigators, and this work yielded the initial
definition of “symptom clusters.”(1)
Initial Definition of Symptom Clusters
• Symptom clusters are three or more concurrent symptoms that
are correlated with each other. The suggested strength of the
relationships has not been specified.
• The symptoms within the cluster are not required to have the
same etiology.
• The amount of time that all of the symptoms within the cluster
need to be present to be considered a “cluster” has not been
specified.
• Symptom clusters have an adverse effect on patient outcomes
and may have a synergistic effect as a predictor of patient
morbidity.(2)
Ongoing Issues of Defining “Symptom Clusters” and Estimating
Prevalence
• Low correlations have been reported among the symptoms in a
cluster with differing etiologies versus higher correlations among
symptoms in a cluster with the same etiology.
• Is the current requirement that the symptoms be correlated
with each other necessary?
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• Can two coexisting, correlated symptoms constitute a “symptom
cluster”?
• Clarity of the role of symptom clusters in predicting adverse
patient outcomes versus the use of clinical variables, e.g.,
comorbidities in predicting coexisting symptoms.
• The use of “cut scores” in determining the existence of any of
the selected symptoms (pain, depression, and fatigue) in a cluster.
The problem of inconsistent “cut scores” across studies. This
problem is an assessment-related issue and will be discussed in
more detail in the assessment section of these proceedings.
Ongoing Studies That Will Elucidate the Occurrence/Prevalence of
Symptom Clusters
Discussion of ongoing studies.
References
1. Dodd MJ, Janson S, Facione N, Faucett J, Froelicher E,
Humphreys J, Lee K, Miaskowski C, Puntillo K, Puntillo K, Rankin S,
Taylor D. Advancing the science of symptom management. J Adv Nurs
2001;33(5):668–76.
2. Dodd MJ, Miaskowski C, Paul S. Symptom clusters and their
effect on the functional status of patients with cancer. Oncol Nurs
Forum 2001;28(3):465–70.
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Assessment of Cancer-Related Symptoms: Pain, Depression, and
Fatigue
William Pirl, M.D.
Literature on the assessment of pain, depression, and fatigue in
people with cancer has been growing over the past decade. The
Evidence-Based Practice Center (EPC) reviewed these studies with
three main goals: (1) identifying instruments that assess all three
symptoms; (2) identifying “gold standard” instruments; and (3)
providing clinical utility data on the instruments.
Methods
A comprehensive search of the medical literature was conducted
to identify relevant studies, with three separate searches for each
symptom. We accepted all studies published in the English language
on patients diagnosed with cancer suffering from pain, depression,
or fatigue. No restrictions were placed on the patients’ age,
gender, ethnicity, level of advancement of the primary disease
(staging), or presence of metastases.
Results
A review of controlled trials that measured pain, depression, or
fatigue in cancer patients yielded 180 studies. Only six
instruments were identified that assessed all three symptoms.
Pain
Many types of instruments have been applied to assess pain and
related analgesic outcomes. Of 218 trials, 125 distinct tools were
employed. By far, the most frequently employed were unidimensional
scales of pain intensity, followed by scales of pain relief, then
measures of peak or summed pain intensity differences between
experimental and control groups. Other tools applied in our group
of studies include global evaluations of efficacy and the
McGill-Melzack pain questionnaire. Also applied were measures of
analgesic consumption and a 4-point side effect scale. Descriptions
of the need for detailed assessment conducted within a psychosocial
framework are presented in virtually all guidelines or monographs
on cancer pain management. A voluminous literature describes the
multidimensional, experiential nature of cancer pain and links poor
control of cancer pain to impaired quality of life, including
functionality. Current expectations for detailed, multidimensional
assessment of cancer pain, including quality of life assessment,
during cancer care contrast with the minimalist assessments of pain
intensity presented during relatively brief observation intervals
reported in nearly all of the trials. Side effects limit analgesic
dosage and hence impede pain control in many patients, yet only 1
of the 16 most widely employed outcomes measures is concerned with
side effects—and that one is a coarse, 4-point measure.
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Depression
The assessment of depression in people with cancer is more
complicated than that of pain and fatigue for two main reasons.
First, depression has overlapping symptoms with cancer and its
treatments. Symptoms common in cancer patients, such as fatigue and
loss of appetite, are part of the Diagnostic and Statistical Manual
of Mental Disorders (DSM) criteria used to make the diagnosis of
major depressive disorder. Because of these overlapping symptoms,
alternative criteria such as the Endicott criteria have been
suggested, substituting some of the more physical symptoms that
could be a function of cancer with more psychological symptoms.
However, there is a very high correlation of diagnoses of major
depressive disorder in cancer patients made with DSM and Endicott
criteria.
The second complication is that depression can refer to a set of
symptoms or clinical syndromes. Although depressive symptoms are
present in several psychiatric disorders, in cancer patients they
are most commonly seen in major depressive disorder, adjustment
disorder with depressed mood, and depression secondary to a general
medical condition. It is the general consensus that a diagnostic
interview that applies the DSM criteria is the standard for
diagnosing major depressive disorder as well as other psychiatric
disorders with depressive symptoms. However, the severity of
depressive symptoms, regardless of diagnosis, can be assessed
through a variety of instruments. These instruments have specified
cutoff points for clinically significant levels of depression. In
more than 150 retrieved studies, the instrument that was used most
often was the Hospital Anxiety and Depression Scale (HADS).
Fatigue
Fifty-six articles were retrieved on the assessment of fatigue.
Numerous patient self-assessment instruments have been used. Most
studies in the last several years have used instruments that assess
multiple dimensions of fatigue and have been tested for validity,
consistency, and reliability. The clinical interpretation of the
outcomes of these instruments remains problematic, however.
Normative fatigue data for non-cancer populations is not usually
available, and it is difficult to compare fatigue measurements
obtained in studies that employ different methodologies and
criteria for fatigue. Strategies for evaluating fatigue in practice
settings have not been the subject of extensive research. The
National Comprehensive Cancer Network has published guidelines on
cancer-related fatigue that include a general approach to
assessment of fatigue in clinical practice. This approach is based
on the experience of a panel of experts rather than controlled
clinical trials, and it has not been validated prospectively.
Future Directions
Because pain, depression, and fatigue commonly occur together in
people with cancer, instruments that assess all three symptoms
should be studied for their validity and clinical utility in each
symptom. Investigations of cancer pain, its assessment, and its
control should seek to evaluate the influence of gender, race, age,
psychosocial context, ethnicity, and culture upon the experience
and report of pain. Consensus recommendations for standardization
of assessment instruments, of both pain and quality of life, must
be developed and implemented in future studies so as to render them
more uniform and, hence, comparable and/or combinable.
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Although there are many instruments being used in research on
depression in patients with cancer, it is unclear how frequently
they may be used in clinical practice. Research is needed on the
clinical use of instruments and their impact on clinical treatment
and outcomes. Studies of promising brief instruments need to be
replicated.
Research is needed to validate approaches for screening and
assessing cancer patients for fatigue in clinical practice. The
development of consensus criteria for the definition and
measurement of cancer-related fatigue would facilitate the
interpretation of research in this area. Studies are needed of the
biological correlates of fatigue, including metabolic, immunologic,
nutritional, and other factors that may shed light on its
etiology.
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Assessment of Pain in Cancer
Charles S. Cleeland, Ph.D.
Numerous studies document that pain due to cancer is
inadequately managed and that existing effective therapies for pain
are not used to maximize pain relief. The result is a high level of
unnecessary distress for patients and families, a significant
impairment in quality of life, and an increased use of health care
systems to treat poorly managed pain on an emergent basis. Factors
that lead to poor pain treatment have been well studied. Patients,
for a variety of reasons, are often reticent to report pain or the
lack of effective treatment. The most significant practice error
that health care professionals make in pain management is
inadequate assessment. When patients are reluctant to report pain,
inadequate assessment becomes even more of a problem for adequate
pain control. Studies of oncology professionals in several
countries demonstrate that these persons are very aware that poor
assessment is the greatest barrier to cancer pain management.
Studies of patients document that one of the strongest predictors
of poor pain management is the discrepancy of pain estimate between
treating doctors and the pain report of patients.
Barriers to pain assessment are many and include a lack of time
for assessment in the clinical encounter, a low priority assigned
to pain management, poor training of health care professionals in
pain management, and a lack of negative sanctions for ineffective
provision of pain control. Clinics rarely provide a protocol for
either pain assessment or management or have care plans in place
for titration of analgesics and adjuvant drugs. Systematic followup
is rare and a special problem when the majority of patients has
developed more severe pain over time due to the progressive nature
of their disease. Minority patients are at greater risk for having
their pain underestimated and their pain inadequately treated.
It can be argued that if pain control were taken seriously as an
element of good cancer care, practice could be improved for the
benefit of patients. Current control methods in place for the
management of infection could provide a model. Infection is
monitored by vital signs, such as fever. If infection is present,
protocols are implemented to deal with it. If monitoring indicates
that the infection is not controlled, the protocol is modified, or
new protocols are put in place. When infection is not controlled,
the health care system treats the situation as very serious, and
there are negative consequences for those who practice. Pain and
symptom management could be viewed in the same way. Pain needs to
become a vital sign, protocols to treat pain need to be in place,
and the effectiveness of pain management needs to be monitored and,
if deficient, corrected. The potential effectiveness of this type
of practice change in pain and symptom assessment needs to be
studied.
The evolution of the scientific basis for pain assessment has
helped advance treatment decision making. This presentation will
present an overview of this progress and the type of clinical
research. New methods for simultaneously monitoring pain together
with other symptoms, such as computer-based telephone queries to
patients at home, can greatly enhance followup and better long-term
symptom control. Better longitudinal data on the time course and
severity of symptoms over time may yield information about
potential mechanisms responsible for these symptoms.
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Assessment of Depression in Cancer Patients
Peter C. Trask, Ph.D.
The diagnostic approach, measures, and inclusion criteria used
to assess symptoms of depression affect conclusions that are drawn
regarding the presence of depression in cancer patients. Assessment
is further affected by individual differences, such as the
patients’ age, gender, race/ethnicity, hospitalization status, and
type and stage of cancer.(1) Finally, the specific assessor and the
timing of the assessment also likely impact conclusions about
depression in cancer patients.
Attempts to identify accurate methods of assessing depression in
cancer patients have employed four different approaches: inclusive,
etiologic, substitutive, and exclusive,(2,3) which vary on whether
somatic symptoms of depression (e.g., weight/appetite, fatigue) are
utilized to arrive at a diagnosis. Using a combination of
approaches is likely to provide a more accurate assessment of
depression than using one alone(4) but may not be possible or
practical, thereby creating a dilemma for researchers and
clinicians wishing to maximize efficiency without sacrificing
diagnostic purity and certainty.
Commonly used approaches to assess depression are structured
clinical interviews and self-report measures. Structured clinical
interviews have traditionally been considered the gold standard for
identifying the prevalence, severity, and need for treatment of
depression, because of their rigorous criteria. They are limited,
however, by their reliance on the diagnostic approach from which
they were developed, validation on nonmedically ill populations,
lengthy administration time, and the amount of training that they
require for proficiency in administration and scoring. As such,
there may be some doubt as to whether such instruments should
indeed be considered the gold standard for all patients, in
particular, for patients with significant medical comorbidities.
The use of self-report measures, by contrast, may be preferred due
to their ease of administration and scoring by individuals who have
not received extensive training and the speed with which they can
be completed by patients. In addition, self-report instruments are
strengthened by their (1) ability to obtain a gross assessment
prior to a direct interview, to quantify severity of depression,
and to identify changes over time and (2) utility in busy
practices. Despite their ease of use and other strengths,
self-report measures do not provide diagnoses and are limited by
their potential to lead to overdiagnosis and high false
positives.
Assessing depression in children and elderly adults (> 65)
with cancer is affected by developmental differences in the
presentation of depression and the potential presence of
complicating comorbidities, such as cognitive impairments or poor
performance status in the elderly. With regard to complicating
factors posed by timing, stage, and treatment status, increased
pain and decreased performance status concomitant with advanced
cancer also impact the assessment of depression. Finally, limited
attention has been paid to the impact that racial, ethnic, and
subcultural differences can have on the assessment of depression in
cancer patients, as the majority of depression measures have been
validated on Caucasian samples.
Two additional issues in the assessment of depression in cancer
patients concern who should assess depression and when. Many
nonpsychiatric health care providers have difficulty
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identifying distress in their patients, in part due to the fact
that many depressed cancer patients are unlikely to report their
symptoms to nonpsychiatric medical staff. In addition, there is a
great deal of variability in the agreement between patient and
staff ratings of depression, strongly suggesting the need for more
research. When to assess is equally as important, as depression by
its very nature varies with time. While preassessments and
postassessments are relatively standard, assessments even earlier
in the course of cancer evaluations may be warranted.(5)
Review of the above issues identifies several areas for future
research, including (1) refining diagnostic criteria for depression
in cancer patients; (2) creating cancer-specific depression
measures with appropriate cutoffs; (3) focusing on the issues of
age, race, ethnicity, subculture, and type and stage of cancer in
creating depression assessment tools; and (4) exploring the issues
of clinical versus subclinical depression, who and when to assess,
and timely and cost-effective ways to assess.
References
1. Aapro M, Cull A. Depression in breast cancer patients: the
need for treatment. Ann Oncol 1999;10:627–36.
2. Cohen-Cole SA, Brown FW, McDaniel JS. Assessment of
depression and grief reactions in the medically ill. In: Stoudemire
A, Fogel BS (eds). Psychiatric care of the medical patient. New
York: Oxford University Press, 1993:53–69.
3. McDaniel JS, Brown FW, Cole SA. Assessment of depression and
grief reactions in the medically ill. In: Stoudemire A, Fogel BS,
Greenberg DB (eds). Psychiatric care of the medical patient. New
York: Oxford University Press, 2000:149–64.
4. Ciaramella A, Poli P. Assessment of depression among cancer
patients: The role of pain, cancer type and treatment.
Psychooncology 2001;10:156–65.
5. Trask PC, Paterson AG, Riba M, Brines B, Griffith K, Parker
P, Weick J, Steele P, Kyro K, Ferrara J. Assessment of
psychological distress in prospective bone marrow transplant
patients. Bone Marrow Transplantation (in press).
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Assessment of Fatigue in Cancer Patients
Paul B. Jacobsen, Ph.D.
Researchers studying fatigue in cancer patients generally agree
that it is a subjective phenomenon best assessed using patients’
own reports. Beyond this, there is no strong consensus about the
optimal measurement approach. As a result, a variety of self-report
techniques are used.
Much of the time, fatigue is assessed using a single item
embedded in a symptom checklist, such as the Symptom Distress Scale
or the Rotterdam Symptom Checklist. Single-item visual analog
scales and Likert-type scales are also often used to assess
fatigue. Due to their format, these single-item measures have
limited reliability and provide only the most perfunctory
information about patients’ experiences with fatigue. Fatigue is
also frequently assessed using multi-item measures, such as Fatigue
Scale of the Profile of Mood States. Although these multi-item
measures generally possess better psychometric properties than
single-item measures, most are limited in that they provide
information only about a patient’s general level of fatigue
severity.
In a more comprehensive approach, several investigators have
developed and validated multidimensional measures of fatigue for
use with cancer patients. Two measures recently developed by our
research group illustrate this approach. The Fatigue Symptom
Inventory is a 14-item measure that consists of separate scales
assessing the intensity and duration of fatigue, as well as its
perceived interference with quality of life. The Fatigue Symptom
Inventory is designed to be used in conjunction with the 30-item
Multidimensional Fatigue Symptom Inventory-Short Form, which
provides information about cognitive, physical, and affective
manifestations of fatigue. Other examples of this multidimensional
approach include the Piper Fatigue Scale and the Brief Fatigue
Inventory. As more studies utilize multidimensional measures, the
advantages of this approach over the unidimensional approach in
furthering our understanding of the experience of fatigue in cancer
patients become increasingly apparent.
The approaches to measuring fatigue described previously share a
common feature: they yield continuous measures of fatigue along one
or more dimensions. In addition to assessing fatigue along a
continuum, it may be possible to identify a set of diagnostic
criteria that can be used to identify the presence of a clinical
syndrome of cancer-related fatigue. An analogy can be drawn to the
assessment of depression. In addition to assessing the severity of
depressive symptomatology along a continuum, it is possible to
identify the presence of a clinical syndrome of major depression
using standard criteria adopted by the American Psychiatric
Association. Based on this model, a group of researchers recently
proposed criteria for the diagnosis of a clinical syndrome of
cancer-related fatigue. Two recent studies have yielded preliminary
empirical support for the reliability and validity of this clinical
syndrome approach.
Several unresolved issues in the assessment of fatigue in cancer
patients should be the focus of future research. One major issue
involves the ability of existing assessment approaches to
distinguish fatigue from depression. Continuous measures of fatigue
and depression administered concurrently to cancer patients
generally yield high positive correlations,
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suggesting possible problems with discriminant validity. A
second issue concerns the use of self-reports of fatigue in
clinical decision-making. Specifically, how should these
self-reports be used to make clinical decisions about initiating
treatments effective in relieving fatigue? A third issue concerns
construct explication and validation. As knowledge accumulates
about the characteristics and causes of fatigue in cancer patients
and its relation to other symptoms, it will be important to use
this information to refine our conceptualization of fatigue and our
approaches to measuring it.
References
Hann DM, Jacobsen PB, Azzarello LM, Martin SC, Curran SL, Fields
KK, Greenberg H, Lyman G. Measurement of fatigue in cancer
patients: development and validation of the Fatigue Symptom
Inventory. Qual Life Res 1998;7:301–10.
Mendoza TR, Wang XS, Cleeland CS, Morrissey M, Johnson BA, Wendt
JK, Huber SL. The rapid assessment of fatigue severity in cancer
patients: use of the Brief Fatigue Inventory. Cancer
1999;85:1186–96.
Piper BF, Dibble SL, Dodd MJ, Weiss MC, Slaughter RE, Paul SM.
The Revised Piper Fatigue Scale: psychometric evaluation in women
with breast cancer. Oncol Nurs Forum 1998;25:677–84.
Sadler IJ, Jacobsen PB, Booth-Jones M, Belanger H, Weitzner MA,
Fields KK. Preliminary evaluation of a clinical syndrome approach
to assessing cancer-related fatigue. J Pain Symptom Manage (in
press).
Stein KD, Martin SC, Hann DM, Jacobsen PB. A multidimensional
measure of fatigue for use with cancer patients. Cancer Pract
1998;6:143–52.
Yellen SB, Cella DF, Webster K, Blendowski C, Kaplan E.
Measuring fatigue and other anemia-related symptoms with the
Functional Assessment of Cancer Therapy (FACT) Measurement System.
J Pain Symptom Manage 1997;13:63-74.
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Assessment: Symptom Clusters
Judith A. Paice, Ph.D., R.N., F.A.A.N.
The control, and ideally prevention, of symptoms such as pain,
depression, and fatigue is dependent upon a comprehensive clinical
assessment. Furthermore, to advance the science of this field,
symptom research requires the use of multidimensional instruments
with proven validity and reliability in a cancer population across
its lifespan. Studies demonstrate a significant correlation between
pain, depression, fatigue, and other symptoms commonly seen
throughout the course of cancer. Therefore, multidimensional scales
incorporating the most common symptoms would ensure systematic
assessment. Optimally, valid and reliable tools that measure
symptom clusters could be feasible for use in both clinical and
research settings. Furthermore, for optimal use, these tools would
be valid for use in a variety of age-specific